VEGF and PDGF are two common and critical pathways implicated in serious retinal diseases and a combination treatment of anti-PDGF and anti-VEGF agents may prove more effective in the treatment of wet AMD than anti-VEGF monotherapy, particularly in recalcitrant disease. This avenue is being investigated by several other companies that are developing their own anti-VEGF/anti-PDGF platforms.

ABICIPAR PEGOL

Designed ankyrin repeat proteins (DARPins) provide a platform for the creation of drugs with multiple binding target proteins, and abicipar pegol (Allergan) is part of this new class of small molecule therapeutics. The company is collaborating with Molecular Partners in the development of an anti-VEGF/anti-PDGF DualDARPin that pairs VEGF-targeting abicipar with another DARPin that targets PDGF for the treatment of patients with AMD.

Two phase 3 studies initiated in 2015 will compare this DualDARPin with ranibizumab (Lucentis, Genentech). These randomized, double-masked, parallel-group, active-controlled studies consist of approximately 400 clinical study sites in roughly 30 countries.

DE-120

DE-120 (Santen) is a small molecule dual tyrosine kinase receptor inhibitor for both VEGF and PDGF signaling pathways. DE-120 belongs to a class of active small molecules that inhibit the activity of receptor tyrosine kinases involved in the angiogenic process. Several such inhibitors have been approved by the FDA and other healthcare authorities for the treatment of various cancers. As a single anti-VEGF/anti-PDGF agent, DE-120 has the potential to provide a synergic antiangiogenic effect and reduce the potential side effects associated with intravitreal injection procedures.

Santen is conducting a phase 2 clinical trial in the United States to evaluate the safety and efficacy of intravitreal DE-120 as monotherapy and along with a single injection of aflibercept (Eylea, Regeneron) in subjects with treatment-naïve active subfoveal CNV secondary to AMD.

TWO MORE BEING INVESTIGATED

Carl C. Awh, MD, and Jeffrey S. Heier, MD, discuss two other anti-VEGF/anti-PDGF combination therapies in this issue: X-82 (Tyrogenex), an orally administered small-molecule tyrosine kinase inhibitor derived from a cancer drug that inhibits VEGF and PDGF receptors here; and REGN2176-3 (Regeneron), which consists of the anti-VEGF drug aflibercept (Eylea, Regeneron) and an antibody to the PDGF receptor (rinucumab, Regeneron) here.